Atividade antiviral de proteínas isoladas de serpentes brasileiras no ciclo replicativo do enterovírus-A71

Abstract

Enteroviruses are a group of viruses that cause several diseases around the world. Among them, Enterovirus A-71 (EV-A71) is the second main cause of Hand, Foot, and Mouth Disease in Asia-Pacific regions. Currently, there are no specific treatments that act directly on the replicative cycle of EV-A71, and, in this context, identifying molecules with antiviral activity is crucial. Proteins isolated from the venom of snakes of the genus Bothrops sp. and Crotalus sp. have demonstrated antiviral, antibacterial, and antiparasitic activity, representing an interesting alternative to the development of therapeutic against EV-A71. Therefore, here we evaluated the anti- EV-A71 potential of the phospholipases A2 MjTX-I e MjTX-II, isolated from Bothrops moojeni, and the proteins crotamine and phospholipase A2CB (PLA-2CB), isolated from Crotalus Durrissus Terrificus. For this, EV-A71 was produced by transfection of the viral RNA in Vero cells, and later titrated by TCID50. To identify the potential of the proteins, EC50 and CC50 were performed by treating Vero cells with the proteins in a serial dilution in the presence or absence of EV-A71 at 100TCID50, respectively. As a result, the proteins MjTX-I, MjTX-II, crotamine and PLA-2CB showed EC50 values of 5.9, 6.3, 8.3 and 4.2 µg/mL, respectively. CC50 values were > 1000 µg/mL for MjTX-I and crotamine, while for MjTX-II and PLA-2CB were 427.6 and 52.3 µg/mL, in that order. In this sense, the evaluated proteins obtained high SI values, being > 170.8 and > 120.4 for MjTX-I and crotamine, respectively, and 67.4 and 12.5 for MjTX-II and PLA-2CB, respectively. To the best of our knowledge, the data presented here demonstrate, for the first time, the inhibitory potential of these proteins against EV-A71, which may result in the prospecting of active molecules and applicable in the medical clinic in the future.